Transmissibility of COVID-19 depends on the viral load around onset in adult and symptomatic patients
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Abstract
To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19).
Methods
Epidemiological and clinical data were obtained from immunocompetent laboratory-confirmed patients with COVID-19 who were admitted to and/or from whom viral loads were measured at Toyama University Hospital. Using a case-control approach, index patients who transmitted the disease to at least one other patient were analysed as “cases” (index patients) compared with patients who were not the cause of secondary transmission (non-index patients, analysed as “controls”). The viral load time courses were assessed between the index and non-index symptomatic patients using non-linear regression employing a standard one-phase decay model.
Results
In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in symptomatic than in asymptomatic patients and in adults than in children. Among symptomatic patients (n = 18), non-linear regression models showed that the estimated viral load at onset was higher in the index than in the non-index patients (median [95% confidence interval]: 6.6 [5.2–8.2] vs. 3.1 [1.5–4.8] log copies/μL, respectively). In adult (symptomatic and asymptomatic) patients (n = 21), median viral load at the initial sample collection was significantly higher in the index than in the non-index patients (p = 0.015, 3.3 vs. 1.8 log copies/μL, respectively).
Conclusions
High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19. Viral load may help provide a better understanding of why transmission is observed in some instances, but not in others, especially among household contacts.
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SciScore for 10.1101/2020.06.02.20120014: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was performed in conformity with the Helsinki Declaration, after approval by the Ethical Review Board of University of Toyama (approval number: R2019167).
Consent: Written informed consent was obtained from all patients.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data were analyzed using JMP Pro version 14.2.0 software (SAS Institute Inc. SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)The viral load time courses were assessed using nonlinear regression employing a standard one-phase decay model in … SciScore for 10.1101/2020.06.02.20120014: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was performed in conformity with the Helsinki Declaration, after approval by the Ethical Review Board of University of Toyama (approval number: R2019167).
Consent: Written informed consent was obtained from all patients.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data were analyzed using JMP Pro version 14.2.0 software (SAS Institute Inc. SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)The viral load time courses were assessed using nonlinear regression employing a standard one-phase decay model in Prism version 8.4.2 ( Prismsuggested: (PRISM, RRID:SCR_005375)GraphPad Software Inc. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has several limitations inherent to the small sample size and potential for confounding viral load and clinical conditions that cannot be excluded. The date of symptom onset and disappearance and information on disease transmission relied on self-reported information from the patients and their families, as well as information from public health centers, which could potentially lead to missing some cases of secondary transmission. In addition, the viral load dynamics were based on data from patients who received treatment, including combinations of antivirals and antibiotics, which could have modified the patterns of the viral load dynamics. In conclusion, the results of this study suggest that a high nasopharyngeal viral load may contribute to the secondary transmission of COVID-19. In addition, the viral load may help explain why transmission is observed in some instances, but not in others, especially among household contacts. Although RT-qPCR does not distinguish between infectious virus and noninfectious nucleic acid, our findings may lead to the establishment of a viral load threshold to clarify COVID-19 disease transmission and infectivity.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.06.02.20120014: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The study was performed in conformity with the Helsinki Declaration , after approval by the Ethical Review Board of University of Toyama ( approval number: R2019167) . Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data were analyzed using JMP Pro version 14.2.0 software ( SAS Institute Inc . SAS Institutesuggested: (Statistical Analysis System, SCR_008567)The viral load time courses were assessed using nonlinear regression employing a standard one-phase decay model … SciScore for 10.1101/2020.06.02.20120014: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The study was performed in conformity with the Helsinki Declaration , after approval by the Ethical Review Board of University of Toyama ( approval number: R2019167) . Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data were analyzed using JMP Pro version 14.2.0 software ( SAS Institute Inc . SAS Institutesuggested: (Statistical Analysis System, SCR_008567)The viral load time courses were assessed using nonlinear regression employing a standard one-phase decay model in Prism version 8.4.2 ( Prismsuggested: (PRISM, SCR_005375)GraphPad Software Inc . GraphPadsuggested: (GraphPad Prism, SCR_002798)Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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